Our objectives are to determine age-related changes in the nervous system as reflected in 1) the activity of the enzymes associated with the formation and degradation of putative neurotransmitters, 2) enzyme synthesis and degradation capability in brain, 3) polyamine metabolism, as another indicator of cellular synthetic activity, 4) biochemical and morphological studies of human cells (i.e., fibroblasts) in culture. The enzymes which are related to putative neurotransmitters and are being studied in selected areas of human brain obtained at autopsy include: tyrosine hydroxylase, DOPA decarboxylase, dopamine-beta-hydroxylase, monoamine oxidase, glutamic acid decarboxylase, choline acetyltransferase, acetylcholinesterase. As an index of de novo enzyme synthesis, studies in animals as a function of age are being conducted in which specific, irreversible inhibitors of enzymes (i.e., monoamine oxidase and acetylcholinesterase) are given and the return of enzymic activity measured. We are also studying ornithine decarboxylase and S-adenosylmethionine decarboxylase depletion by starvation and subsequent return of enzyme activity on feeding in young and old mice. Enzyme activity (i.e., glutamic acid decarboxylase) is being compared with the number of molecules of that enzyme measured by immunoassay, to assess the catalytic efficiency as a function of age in discrete regions of animal and human brain. Human cell culture studies are being done in which the morphology, motility, rate of protein synthesis and degradation, and the metabolism of polyamines are being investigated as related to the age of the cultures.